No abstract

The 10th Banff Conference on Allograft Pathology was held in Banff, Canada from August 9 to 14, 2009. A total of 263 transplant clinicians, pathologists, surgeons, immunologists and researchers discussed several aspects of solid organ transplants with a special focus on antibody mediated graft injury. The willingness of the Banff process to adapt continuously in response to new research and improve potential weaknesses, led to the implementation of six working groups on the following areas: isolated v-lesion, fibrosis scoring, glomerular lesions, molecular pathology, polyomavirus nephropathy and quality assurance. Banff working groups will conduct multicenter trials to evaluate the clinical relevance, practical feasibility and reproducibility of potential changes to the Banff classification. There were also sessions on quality improvement in biopsy reading and utilization of virtual microscopy for maintaining competence in transplant biopsy interpretation. In addition, compelling molecular research data led to the discussion of incorporation of omics-technologies and discovery of new tissue markers with the goal of combining histopathology and molecular parameters within the Banff working classification in the near future.

SummaryWithin 1 wk ofliqnid culture in granulocyte/macrophage colony-stimulating factor (GM-CSF), normal B10 BR (H-2 k I-E +) mouse liver nonparenchymal cells (NPC) formed loosely adherent mydoid cell clusters that have been shown to contain dendritic cell (DC) progenitors in similar studies of mouse blood or bone marrow. Mononuclear cell progeny released from these clusters at and beyond 4 d exhibited distinct dendritic morphology and were actively phagocytic. After 6-10 d of culture, these cells strongly expressed CD45, CDllb, heat stable antigen, and CD44. However, the intensity of expression of the DC-restricted markers NLDC 145, 33D1, and N418, and the macrophage marker F4/80, intercellular adhesion molecule 1, and Fc~RII was low to moderate, whereas the cells were negative for CD3, CD45RA, and NKI.1. Splenocytes prepared in the same way also had a similar range and intensity of expression of these immunophenotypic markers. Unlike the splenic DC, however, most of the GM-CSF-propagated putative liver DC harvested at 6-10 d expressed only a low level of major histocompatibility complex (MHC) class II (I-Ek), and they failed to induce primary allogeneic responses in naive T cells, even when propagated additionally in GM-CSF and tumor necrosis factor ot and/or interferon V-supplemented medium. However, when 7-d cultured GM-CSF-stimulated liver cells were maintained additionally for three or more days on type-1 collagen-coated plates in the continued presence of GM-CSF, they exhibited characteristics of mature DC: MHC class II expression was markedly upregulated, mixed leukocyte reaction stimulatory activity was increased, and phagocytic function was decreased. Similar observations were made when Ia + cells were depleted from the GM-CSF-propagated cells before exposure to collagen. Further evidence that the GM-CSF-stimnlated class II ~ or dass II-depleted hepatic NPC were immature DC was obtained by injecting them into allogeneic B10 (H-2 s I-E-) recipients. They "homed" to T cell-dependent areas of lymph nodes and spleen where they strongly expressed donor MHC dass II antigen 1-5 d later. These observations provide insight into the regulation of DC maturation, and are congruent with the possibility that the migration of immature DC from normal liver and perhaps other organ allografrs may help explain their inherent tolerogenicity.

Surgical weight loss results in significant improvement of liver morphology in severely obese patients. These beneficial changes may be associated with a significant reduction in the prevalence of the metabolic syndrome.

Advances in the management of both chronic and acute hepatic disease have been made possible and even mandated by the development of liver transplantation. The clinical use of transplantation has proceeded at a rapid pace since a Consensus Development Conference of the National Institutes of Health concluded in June 1983 that liver transplantation had become a service and not simply an experimental procedure. 1 The liver can be transplanted as an extra (auxiliary) organ at an ectopic site, or in the orthotopic location after the removal of the host liver (Fig. 1). This article will focus primarily on the orthotopic procedure. However, there has been renewed interest in the auxiliary operation, which will be discussed separately. Candidacy for TransplantationThe conceptual appeal of liver transplantation is so great that the procedure may come to mind as a last resort for virtually every patient with lethal hepatic disease. The selection of appropriate recipients from such a large pool requires strict individual assessment. A 1982 estimate of the annual need for liver transplantation was 15 per million population, 2 but the current need is undoubtedly higher because there are now fewer restrictions on candidacy. Between 4000 and 50,000 liver transplantations a year may be needed in the United States.The supply of organs will increasingly influence the criteria for candidacy and limit the use of the procedure. Discussions about rationing transplantation services for this reason are nonetheless premature, because the balance between need and supply has not been determined. In the United States, the yearly rate of liver transplantation has reached approximately 1600; it averaged 147 a month between July and December 1988 (Vaughn W, United Network of Organ Sharing: personal communication). The annual rate in Europe approaches this figure.Policies on organ donation will have to be reexamined if substantial growth is to occur. Many potential liver donors are probably rejected unjustifiably. The arbitrary upper age limit observed by most programs 3 cannot be justified, because senescence largely spares the liver. 4 Atherosclerosis of the hepatic arteries is not usually found beyond the origin of the celiac axis. 4 Our own limited experience with livers from donors over 50 years old has been encouraging.